Cancer of the endometrium is the most common gynecologic malignancy and accounts for 6% of all cancers in women. It is estimated that there were over 39,000 new cases and approximately 7,400 deaths due to endometrial (uterine corpus) cancer in the United States in 2007. The cancer is considered a highly curable tumor. Endometrial cancer usually develops after menopause, between the ages of 50 and 60. Because it is usually associated with postmenopausal bleeding, this kind of cancer is often found at its earliest stage, when it is highly curable.
A number of factors have been found to increase a women's risk of developing endometrial cancer. One of the primary factors is unopposed estrogen replacement therapy/hormone therapy or tamoxifen therapy. There also appears to be genetic factors that increase the likelihood of disease, with the disease running in families.
Over 75% of endometrial cancers are adenocarcinomas. These form in the glandular cells located on the endometrium lining. Endometrioid adenocarcinomas are usually detected early and have a high rate of cure. About 10 percent of endometrial cancers are papillary serous adenocarcinomas, and 5 percent are clear cell adenocarcinomas. Both papillary serous adenocarcinomas and clear cell adenocarcinomas are more-aggressive types of endometrial cancer. They are more likely to recur or metastasize to another part of the body. Other types of endometrial cancer include adenosquamous carcinomas, which have elements of both adenocarcinoma and squamous cell carcinoma, and adenoacanthomas, in which squamous cells appear benign and glandular cells appear cancerous.
Four types of treatment for endometrial cancer have been proposed; surgery (including total hysterectomy, bilateral salpingo-oophorectomy, and radical hysterectomy), chemotherapy, radiation therapy, and hormone therapy. The choice of treatment is dictated by the stage of cancer.
MicroRNAs (miRNAs) are a new class of RNA's. Although they were first discovered in 1993, it has only been in the past few years that a more detailed understanding of their function and implications has begun to evolve. They are ˜20-25 nucleotides in length. They function to regulate gene expression by inhibiting translation at the transcriptional and post-transcriptional level and degrading specific mRNAs. Growing evidence indicates that miRNAs are involved in proliferation, differentiation, apoptosis, growth, and development. They are further associated with control of oncogenes and tumor suppressor genes and are often found in fragile genomic regions involved in cancer. More than 200 miRNAs have been implicated in human carcinogenesis. Analysis of microRNA expression has shown that microRNA profiles could be of value in cancer diagnosis. A global downregulation of microRNA has been observed in tumors, and the microRNA profile also been shown to reflect the origin and differentiation state of the tumor.
Predicting the responsiveness of a tumor to a particular therapy has proven elusive. It would be highly advantageous to have refined methods of predicting the response to cancer treatment. For instance, in the case of chemotherapy, it would be highly desirable to be able to structure treatment regimens that allow a subject to avoid exposure to potentially toxic therapies that may derive little or no benefit to the patient in curing their condition. Similarly, methods of tailoring the optimal treatment regime could be effected where a timely and reliable system for predicting response is available to practitioners. The present invention solves this and other important needs in the art as will be apparent in the following.